Novel compounds

ABSTRACT

Insecticidal compounds of formula (I) &lt;CHEM&gt; wherein R&lt;1&gt; and R&lt;2&gt; are independently selected from halogen or nitro; R&lt;3&gt; and R&lt;4&gt; are independently selected from hydrogen or halogen; R&lt;5&gt; is hydrogen, halogen or cyano; and R&lt;6&gt; is halogen or haloalkyl; provided that R&lt;1&gt;, R&lt;2&gt;, R&lt;3&gt; and R&lt;4&gt; are not all fluorine.

The present invention relates to novel phenyl pyrimidinone derivativeswhich have insecticidal activity, to processes for their preparation andto their use as insecticides.

Canadian Patent No 888730 discloses certain herbicidal compounds offormula: ##STR2## Where R^(a) is inter alia halo or nitro; R^(b) isinter alia optionally substituted phenyl and R^(c) is inter aliahydrogen. However no specific examples of substituted phenyl groupsR^(b) are disclosed.

According to the present invention there is provided a compound offormula (I) ##STR3## wherein R¹ and R² are independently selected fromhalogen or nitro; R³ and R⁴ are independently selected from hydrogen orhalogen; R⁵ is hydrogen, halogen or cyano; and R⁶ is halogen orhaloalkyl; provided that R¹, R², R³ and R⁴ are not all fluorine.

Suitable halogen groups for R¹, R², R³, R⁴, R⁵ and R⁶ include fluoro,chloro, bromo or iodo.

Preferably at least one of R¹ or R² is halo. In particular R¹ and R² areboth fluoro or chloro.

Suitably R³ and R⁴ are hydrogen.

In preferred embodiments R¹, R², R³ and R⁴ are not all halo.

Suitably R⁵ is hydrogen or halogen. Most preferably R⁵ is hydrogen,chlorine, or bromine.

Suitable haloalkyl groups R⁶ contain straight or branched chain alkylgroups suitably having from 1 to 6 carbon atoms. Particular haloalkylgroups are di-or trihalomethyl groups, such as trifluoromethyl ordifluoromethyl or pentahaloethyl groups such as pentafluoroethyl.

A preferred sub-groups of compounds of formula (I) are compounds offormula (IA) ##STR4## where one of R^(1') or R^(2') is halo and theother is halo in particular fluorine, chlorine or bromine or nitro;R^(5') is hydrogen or halogen in particular chlorine or bromine; andR^(6') is trifluoromethyl or pentafluoroethyl.

Examples of compounds of formula (I) are set out in Table I below.

                  TABLE I                                                         ______________________________________                                        COMPOUND NO.                                                                              R.sup.1 R.sup.2 R.sup.3                                                                            R.sup.4                                                                            R.sup.5                                                                            R.sup.6                            ______________________________________                                         1          Cl      Cl      H    H    H    CF.sub.3                            2          Cl      NO.sub.2                                                                              H    H    H    CF.sub.3                            3          NO.sub.2                                                                              NO.sub.2                                                                              H    H    H    CF.sub.3                            4          F       Cl      H    H    H    CF.sub.3                            5          Br      Cl      H    H    H    CF.sub.3                            6          Br      Br      H    H    H    CF.sub.3                            7          Cl      NO.sub.2                                                                              H    H    F    CF.sub.3                            8          Cl      NO.sub.2                                                                              H    H    Br   CF.sub.3                            9          Cl      Cl      H    H    Br   CF.sub.3                           10          Cl      I       H    H    H    CF.sub.3                           11          F       F       H    H    H    CF.sub.3                           12          CL      NO.sub.2                                                                              H    H    Cl   CF.sub.3                           13          Cl      Cl      H    H    Cl   CF.sub.3                           14          Cl      NO.sub.2                                                                              H    H    I    CF.sub.3                           15          NO.sub.2                                                                              NO.sub.2                                                                              H    H    Br   CF.sub.3                           16          NO.sub.2                                                                              NO.sub.2                                                                              Cl   H    H    CF.sub.3                           17          Cl      NO.sub.2                                                                              H    H    H    C.sub.2 F.sub.5                    18          Cl      Cl      H    H    H    C.sub.2 F.sub. 5                   19          F       Cl      H    H    Br   CF.sub.3                           20          F       NO.sub.2                                                                              H    H    H    CF.sub.3                           21          NO.sub.2                                                                              Br      H    H    H    CF.sub.3                           22          F       Cl      H    H    Cl   CF.sub.3                           23          F       F       H    H    Br   CF.sub.3                           24          NO.sub.2                                                                              NO.sub.2                                                                              H    H    Cl   CF.sub.3                           25          Br      NO.sub.2                                                                              H    H    Cl   CF.sub.3                           26          Br      NO.sub.2                                                                              H    H    Br   CF.sub.3                           27          Cl      NO.sub.2                                                                              H    H    CN   CF.sub.3                           28          Cl      Cl      H    H    CN   CF.sub.3                           29          Cl      NO.sub.2                                                                              H    H    Br   C.sub.2 F.sub.5                    30          Cl      Br      H    H    Br   CF.sub.3                           31          Br      Br      H    H    Cl   CF.sub.3                           32          Br      Br      H    H    Br   CF.sub.3                           33          Cl      Cl      H    H    Br   C.sub.2 F.sub.5                    34          Cl      Br      H    H    Cl   CF.sub.3                           35          Cl      Cl      H    H    H    Cl                                 36          Cl      NO.sub.2                                                                              H    H    H    Cl                                 37          Cl      NO.sub.2                                                                              H    H    Cl   C.sub.2 F.sub.5                    38          F       Cl      H    H    H    C.sub.2 F.sub.5                    39          F       F       H    H    Cl   CF.sub.3                           40          F       Cl      H    H    Br   C.sub.2 F.sub.5                    41          Cl      NO.sub.2                                                                              H    H    H    CF.sub.2 H                         42          Cl      Br      H    H    H    C.sub.2 F.sub.5                    43          Cl      Br      H    H    Br   C.sub.2 F.sub.5                    44          Br      NO.sub.2                                                                              H    H    H    C.sub.2 F.sub.5                    45          Br      Br      H    H    H    C.sub.2 F.sub.5                    46          Cl      Cl      H    H    Cl   C.sub.2 F.sub.5                    47          Br      Br      H    H    Br   C.sub.2 F.sub.5                    ______________________________________                                    

Compounds of formula (I) can be prepared by reacting a compound offormula (II) ##STR5## wherein R¹, R², R³ and R⁴ are as defined inrelation to formula (I) and R⁷ is a leaving group; with a compound offormula (III) ##STR6## wherein R⁵ and R⁶ are as defined in relation toformula (I); and thereafter if desired carrying out one or more of thefollowing steps: (i) converting the group R⁵ where it is hydrogen, todifferent group R⁵ ; or (ii) converting a group R¹, R², R³ or R⁴ to adifferent such group.

The reaction is suitably carried out in the presence of a solvent and abase. The base may be for example an alkali metal hydride, an alkalimetal alkoxide or an alkali metal carbonate, and the solvent may be ahydrocarbon solvent, such as petroleum ether, an alcohol or an aproticpolar solvent such as dimethylformamide or dimethylacetamide.

Suitable leaving groups R⁷ include halo groups such as fluoro, chloro,bromo or iodo.

If necessary an appropriate catalyst such as a crown ether or copper canbe added depending upon the precise nature of R⁷. Further details of theprocesses for preparation of the compounds may be ascertaned from theExamples set out hereinafter.

Conversion of the group R⁵ from hydrogen into a halogen group such asbromine or chloro as in optional step (i) above can be carried out byreacting the compound of formula (I) where R⁵ is hydrogen with a halogensuch as bromine in the presence of a base such as sodium acetate. Thereaction is suitably carried out in an organic solvent such as aceticacid at moderate temperatures of from 0°-50° C., conveniently at ambienttemperature.

Alternatively the conversion can be carried out using other knownhalogenating agents such as N-bromosuccinimide or N-chlorosuccinimide inan organic solvent such as acetonitrile or dimethylformamide. Suitablyelevated temperatures of from 60° to 100° C. are employed.

Optional step (ii) above may also be carried out by conventional means.For example compounds of formula (I) wherein R¹ and/or R² is nitro canbe converted to the corresponding compound of formula (I) wherein R¹and/or R² is halo by reduction of the nitro groups to an amino group toform a compound of formula (IV): ##STR7## wherein R³, R⁴, R⁵ and R⁶ areas defined in relation to formula (I) and R⁸ and R⁹ are amino or a groupR¹ or R² as defined in relation to formula (I) provided that at leastone of R⁸ or R⁹ is amino; and thereafter converting the amino group R⁸and/or R⁹ to halo.

Compounds of formula (IV) are novel and as such form a further aspect ofthe invention.

Reduction of the nitro groups to form a compound of formula (IV) can becarried out by reacting the compound with a reducing agent such asstannous chloride in acid conditions, for example in a solution inconcentrated hydrochloride acid. Moderate temperatures of from 2° to 45°C. are suitably employed.

Subsequent halogenation may be carried out by reaction witht-butylnitrite and a copper halide salt such as copper (I)iodide. Thisstep is suitably carried out in an organic solvent such as acetonitrileat low temperatures of from -20° to +20° C. preferably at about 0° C.

Compounds of formula (III) can be prepared by reacting a compound offormula (V) ##STR8## wherein R¹⁰ is hydrogen or C₁₋₄ alkyl such as ethylwith Raney Nickel in an appropriate solvent such as aqueous ammonia.

Compounds of formula (V) are either known compounds or they can beprepared from known compounds by known methods (see for example AGiner-Sorolla, A Bendick: J. Am. Chem, Soc, 1958, 80, 5744).

Some compounds of formula (II), (III) and (V) are novel and these form afurther aspect of the invention. Therefore further according to thepresent invention there is provided a compound of formula (IIA) ##STR9##wherein R¹¹ is chlorine, R¹² is fluorine and R¹³ is iodine, or R¹¹ isnitro, R¹² is bromo and R¹³ is bromo.

The compound of formula (IIA) where R¹¹ is chlorine, R¹² is fluorine andR¹³ is iodine can be prepared from the compound of formula (II) where R¹is chlorine, R² is nitro, R⁷ is fluorine and R³ and R⁴ are hydrogen byreduction of the group R² to amino and subsequent halogenating to thedesired compound of formula IIA using methods analogous to thosedescribed above in relation to optional step (ii) for the preparation ofthe compounds of formula (I).

The intermediate compound of formula (VI): ##STR10## is novel and formsa further aspect of the invention.

Novel compounds of formula (III) are compounds of formula (IIIA)##STR11## wherein R¹³ is hydrogen, halogen or cyano and R¹⁴ is halo orhaloalkyl with the proviso that (a) when R¹³ is cyano, R¹⁴ is other thanchlorine; (b) R¹³ and R¹⁴ are not both halo; (c) when R¹³ is halo, R¹⁴is other than monofluoromethyl; and (d) when R¹³ is hydrogen, R¹⁴ is nothalo or a halomethyl group.

A particular example of R¹⁴ is pentafluoroethyl.

Compounds of formula (IIIA) can be prepared by various routes includingpreparation from the appropriate compound of formula (V) as describedabove. Alternatively the compound of formula (IIIA) can be prepared fromthe appropriate compound of formula (III) where R⁵ is hydrogen byhalogenation using for example conditions similar to those describedabove in relation to the conversion of R⁵ from hydrogen to halogen.Compounds of formula (IIIA) where R¹³ is cyano can be prepared byreacting a compound of formula (III) where R⁵ is bromine with a cyanidesalt such as copper (I) cyanide in an organic solvent such as quinolineat elevated temperature of from 200° to 250° C.

Novel compounds of formula (V) are compounds of formula (VA): ##STR12##wherein R¹⁰ is as defined in relation to formula (V), R¹⁵ is cyano andR¹⁶ is R⁶ as defined in relation to formula (V) or R¹⁵ is hydrogen orhalogen other than fluorine and R¹⁶ is pentafluoroethyl ordifluoromethyl.

Compounds of formula (VA) can be prepared by reacting a compound offormula (VII): ##STR13## wherein R¹⁵ and R¹⁶ are as defined in relationto formula (VA) and R¹⁷ is a C₁₋₆ alkyl group with thiourea or anappropriate alkylated derivative thereof in the presence of a strongbase such as an alkali metal alkoxide such as sodium methoxide. Elevatedtemperatures of from 60° C. to 90° C. are suitably employed.

Other compounds of formula (II), (III) and (V) and compounds of formula(VII) are either known compounds or they can be prepared from knowncompounds by conventional methods.

The compounds of formula (I) may be used to combat and controlinfestations of insect pests and also other invertebrate pests, forexample, acarine pests. The insect and acarine pests which may becombatted and controlled by the use of the invention compounds includethose pests associated with agriculture (which term includes the growingof crops for food and fibre products), horticulture and animalhusbandry, forestry, the storage of products of vegetable origin, suchas fruit, grain and timber, and also those pests associated with thetransmission of diseases of man and animals.

Compounds of formula (I) are particularly useful against public healthpests such as cockroaches and houseflies.

In order to apply the compounds to the locus of the pests they areusually formulated into compositions which include in addition to theinsecticidally active ingredient or ingredients of formula I suitableinert diluent or carrier materials, and/or surface active agents. Thecompositions may also comprise another pesticidal material, for exampleanother insecticide or acaricide, or a fungicide, or may also comprisean insecticide synergist, such as for example dodecyl imidazole,safroxan, or piperonyl butoxide.

The compositions may be in the form of dusting powders wherein theactive ingredient is mixed with a solid diluent or carrier, for examplekaolin, bentonite, kieselguhr, or talc, or they may be in the form ofgranules, wherein the active ingredient is absorbed in a porous granularmaterial for example pumice.

Alternatively the compositions may be in the form of liquid preparationsto be used as dips or sprays, which are generally agueous dispersions oremulsions of the active ingredient in the presence of one or more knownwetting agents, dispersing agents or emulsifying agents (surface activeagents).

Wetting agents, dispersing agents and emulsifying agents may be of thecationic, anionic or non-ionic type. Suitable agents of the cationictype include, for example, quaternary ammonium compounds, for examplecetyltrimethyl ammonium bromide. Suitable agents of the anionic typeinclude, for example, soaps, salts of aliphatic monoesters of sulphuricacid, for example sodium lauryl sulphate, salts of sulphonated aromaticcompounds, for example sodium dodecylbenzenesulphonate, sodium, calciumor ammonium lignosulphonate, or butylnaphthalene sulphonate, and amixture of the sodium salts of diisopropyl- and triisopropylnaphthalenesulphonates. Suitable agents of the non-ionic type include, for example,the condensation products of ethylene oxide with fatty alcohols such asoleyl alcohol or cetyl alcohol, or with alkyl phenols such as octylphenol, nonyl phenol and octyl cresol. Other non-ionic agents are thepartial esters derived from long chain fatty acids and hexitolanhydrides, the condensation products of the said partial esters withethylene oxide, and the lecithins.

The compositions may be prepared by dissolving the active ingredient ina suitable solvent, for example, a ketonic solvent such as diacetonealcohol, or an aromatic solvent such as trimethylbenzene and adding themixture so obtained to water which may contain one or more knownwetting, dispersing or emulsifying agents.

Other suitable organic solvents are dimethyl formamide, ethylenedichloride, isopropyl alcohol, propylene glycol and other glycols,diacetone alcohol, toluene, kerosene, white oil, methylnaphthalene,xylenes and trichloroethylene, N-methyl-2-pyrrolidone andtetrahydrofurfuryl alcohol (THFA).

The compositions which are to be used in the form of agueous dispersionsor emulsions are generally supplied in the form of a concentratecontaining a high proportion of the active ingredient or ingredients,the said concentrate to be diluted with water before use. Theseconcentrates are often required to withstand storage for prolongedperiods and after such storage, to be capable of dilution with water toform agueous preparations which remain homogenous for a sufficient timeto enable them to be applied by conventional spray equipment. Theconcentrates may contain 10-85% by weight of the active ingredient oringredients. When diluted to form agueous preparations such preparationsmay contain varying amounts of the active ingredient depending upon thepurpose for which they are to be used. For agricultural or horticulturalpurposes, an agueous preparation containing between 0.0001% and 0.1% byweight of the active ingredient (approximately equivalent to from 5-2000g/ha) is particularly useful.

In use the compositions are applied to the pests, to the locus of thepests, to the habitat of the pests, or to growing plants liable toinfestation by the pests, by any of the known means of applyingpesticidal compositions, for example, by dusting or spraying.

The compounds of the invention may be the sole active ingredient of thecomposition or they may be admixed with one or more additional activeingredients such as insecticides, insecticide synergists, herbicides,fungicides or plant growth regulators where appropriate. Suitableadditional active ingredients for inclusion in admixture with thecompounds of the invention may be compounds which will broaden thespectrum of activity of the compounds of the invention or increase theirpersistence in the location of the pest. They may synergise the activityof the compound of the invention or complement the activity for exampleby increasing the speed of effect, improving knockdown or overcomingrepellency. Additionally multi-component mixtures of this type may helpto overcome or prevent the development of resistance to individualcomponents. The particular insecticide, herbicide or fungicide includedin the mixture will depend upon its intended utility and the type ofcomplementary action required. Examples of suitable insecticides includethe following:

a) Pyrethroids such as permethrin, esfenvalerate, deltamethrin,cyhalothrin in particular lamda-cyhalothrin, biphenthrin, fenpropathrin,cyfluthrin, tefluthrin, fish safe pyrethroids for example etofenprox,natural pyrethrin, tetramethrin, s-bioallethrin, fenfluthrin,prallethrin and 5-benzyl-3-furylmethyl-(E)-(1R,3S)-2,2-dimethyl-3-(2-oxothiolan-3-ylidenemethyl) cyclopropanecarboxylate;

b) Organophosphates such as profenofos, sulprofos, methyl parathion,azinphos-methyl, demeton-s-methyl, heptenophos, thiometon, fenamiphos,monocrotophos, profenophos, triazophos, methamidophos, dimethoate,phosphamidon, malathion, chloropyrifos, phosalone, fensulfothion,fonofos, phorate, phoxim, pyrimiphos-methyl, fenitrothion or diazionon;

c) Carbamates (including aryl carbamates) such as pirimicarb,cloethocarb, carbofuran, ethiofencarb, aldicarb, thiofurox, carbosulfan,beniocarb, fenobucarb, propoxur or oxamyl;

d) Benzoyl ureas such as triflumeron, or chlorofluazuron;

e) Organic tin compounds such as cyhexatin, fenbutatin oxide,azocyclotin;

f) Macrolides such as avermectins or milbemyins, for example such asavamectin, avermectin, and milbemycin;

g) Hormones such as pheromones;

h) Organochlorine compounds such as benzene hexachloride, DDT, chlordaneor dieldrin.

i) Amidines, such as chlordimeform or amitraz.

In addition to the major chemical classes of insecticide listed above,other insecticides having particular targets may be employed in themixture if appropriate for the intended utility of the mixture. Forinstance selective insecticides for particular crops, for examplestemborer specific insecticides for use in rice such as cartap orbuprofezin can be employed. Alternatively insecticides specific forparticular insect species/stages for example ovo-larvicides such asclofentezine, flubenzimine, hexythiazox and tetradifon, moltilicidessuch as dicofol or propargite, acaricides such as bromopropylate,chlorobenzilate, or growth regulators such as hydramethylon, cyromazin,methoprene, chlorofluazuron and diflubenzuron may also be included inthe compositions.

Examples of suitable insecticide synergists for use in the compositionsinclude piperonyl butoxide, sesamax, and dodecyl imidazole.

Suitable herbicides, fungicides and plant-growth regulators forinclusion in the compositions will depend upon the intended target andthe effect required.

An example of a rice selective herbicides which can be included ispropanil, an example of a plant growth regulator for use in cotton is"Pix", and examples of fungicides for use in rice include blasticidessuch as blasticidin-S.

The ratio of the compound of the invention to the other activeingredient in the composition will depend upon a number of factorsincluding type of target, effect required from the mixture etc. Howeverin general, the additional active ingredient of the composition will beapplied at about the rate as it is usually employed, or at a slightlylower rate if synergism occurs.

The compounds of formula I and compositions comprising them have shownthemselves active against a variety of insect and other invertebratepests. They are particularly useful in controlling public health pestssuch as flies and cockroaches. They may also be active againstorganophosphate and pyrethroid resistant strains of pests such ashouseflies (Musca domestica). They may be effective in combating bothsusceptible and resistant strains of the pests in their adult, larvaland intermediate stages of growth, and may be applied to the infestedhost animal by topical, oral or parenteral administration.

The following Preparations and Examples are given by way ofillustration.

PREPARATION 1

This description illustrates the preparation of4-pentafluoroethyl-2-thiouracil.

Thiourea (3 g) was added to a solution of sodium methoxide in methanol(previously prepared by adding sodium metal (1.089 g) to dry methanol(20 ml)). This was followed by ethyl pentafluoropropionyl acetate (9.61g) and the reaction mixture was heated under reflux for 3 days. Aftercooling the solvent was evaporated, in vacuo, to give a brown solid,which was acidified with dilute agueous hydrochloric acid and extractedwith diethyl ether. The combined organic extracts were dried, andremoval of the solvent by evaporation, under reduced pressure, gave4-pentafluoroethyl-2-thiouracil (4.14 g), which was immediately carriedto the next stage;

'H NMR δ (CDCl₃) 12.3(1H, brs), 11.65 (1H, brs) and 6.2(1H,s).

PREPARATION 2

This description illustrates the preparation of4-pentafluoroethylpyrimidin-6-one.

Raney Nickel (0.83 g, of a 50% dispersion in water) was added to asuspension of 4-pentafluoroethyl-2-thiouracil (0.5 g) in a mixture ofconcentrated agueous ammonia (0.23 ml) in water (6 ml). The reactionmixture was heated to reflux for 5.5 hours, cooled, stood overnight, andfiltered hot through hyflo. The filterate was concentrated byevaporation of the solvent under reduced pressure to give the desiredcompound as a pale green solid. Sublimation (100° C., 0.1 mbar) gave4-pentafluoroethylpyrimidin-6-one as a white solid mpt 122°-126° C.;

'H NMR δ (CDCl₃) 13.05 (1H, brs) 8.30 (1H,s) and 6.94 (1H,s).

PREPARATION 3

This description illustrates the preparation of5-bromo-4-trifluoromethylpyrimidin-6-one.

Bromine (4.62 g) was added in one portion to a stirred solution of4-trifluoromethylpyrimidin-6-one (4.3 g) and sodium acetate (10.53 g) inacetic acid (43 ml). After stirring for 2 hours, the reaction mixturewas left to stand for a period of 3 days, after which time it was heatedto 80° C. for 1 hour. After cooling to the ambient temperature (ca 22°C.), the solvent was evaporated under reduced pressure. The resultantorange solid was dissolved in ethyl acetate, and washed several timeswith water. The combined agueous washings were extracted withethylacetate, and the combined organic layers were washed with agueoussodium thiosulphate solution, followed by agueous sodium bicarbonatesolution and brine. After drying over magnesium sulphate, evaporation ofthe solvent under reduced pressure gave5-bromo-4-trifluoromethylpyrimidin-6-one as a white solid (4.8 g, mpt226°-227° C.);

'H NMR δ (CDCl₃), 8.05(s); ¹⁹ F NMR δ (CDCl₃), -67.4(s).

PREPARATION 4

This description illustrates the preparation of5-iodo-4-trifluoromethylpyrimidin-6-one.

N-Iodosuccinimide (2.75 g) was added to a stirred suspension of4-trifluoromethylpyrimidin-6-one (1 g) in dry acetonitrile (13 ml). Thereaction mixture was stirred at the ambient temperature for 2 hours, andthen heated under reflux for 10 hours. After cooling, removal of thesolvent under reduced pressure gave a brown solid which wasrecrystallised from water to give5-iodo-4-trifluoromethylpyrimidin-6-one as a pale orange solid (150 mg);

'H NMR δ (CDCl₃ +3 drops DMSO) 13.5 (1H, brs) and 8.00 (1H,s).

PREPARATION 5

This description illustrates the preparation of5-chloro-4-trifluoromethylpyrimidin-6-one.

N-chlorosuccinide (6.56 g) was added to a stirred suspension of4-trifluoromethylpyrimidin-6-one (4 g) in dry acetonitrile (50 ml), andthe mixture heated under reflux for 17 hours. After cooling, the thesolvent was removed by evaporation under reduced pressure to give awhite solid which was recrystallised from water (twice) to give5-chloro-4-trifluoromethylpyrimidin-6-one as a white solid (1.06 g, mpt191°-192° C.)

'H NMR δ (CDCl₃ +1 drop DMSO) 13.5 (1H, brs) and 8.05 (1H, d).

PREPARATION 6

This description illustrates the preparation of5-cyano-4-trifluoromethylpyrimidin-6-one.

Copper(I)cyanide (80 mg) was added to a solution of5-bromo-4-trifluoromethylpyrimidin-6-one (150 mg) in quinoline (5 ml).The reaction mixture was then heated to the reflux temperature for aperiod of 3 hours. After cooling to the ambient temperature, thereaction mixture was pured into dilute agueous acetic acid, andextracted into ethyl acetate. After drying, evaporation of the solventunder reduced pressure gave a brown oil, which was subjected tochromatography on silica gel plates using ethylacetate containing aceticacid and water (250:5:1 by volume) as eluent. The desired fraction wascollected, and the brown solid thus isolated was identified as aphenolic salt. This material was dissolved in ethanol, and acidifiedwith ethanolic hydrogen chloride. Evaporation of the solvent underreduced pressure gave a brown solid which was dissolved in diethyl etherand filtered. Evaporation of the solvent under reduced pressure gave5-cyano-4-trifluoromethyl-pyrimidin-6-one as a brown solid.

IR (Nujol mull) 3100, 2920, 2235, 1730, 1700, 1680, 1600, 1440, 1330,1210, 1160, 1130 and 958 cm^(-') ;

'H NMR δ (DMSO) 8.70 (1H,s), 3.45 (1H, brs).

PREPARATION 7

This description illustrates the preparation of3,4-difluoro-5-nitrotrifluoromethylbenzene.

A mixture of 4-chloro-3,5-dinitrotrifluoromethylbenzene (10 g) and drypotassium fluoride (4.3 g) in dry dimethylformamide (25 ml) was stirredvigorously and heated to 100° C. for 16 hours. After cooling to ambienttemperature, further potassium fluoride (2.15 g) was added, and themixture was heated to 130° C. for 2 days. After cooling, the reactionmixture was poured into water, and extracted with diethyl ether. Theorganic layer was dried, filtered, and the solvent removed byevaporation, under reduced pressure. The residual oil was subjected tokugelrohr distillation under reduced pressure to give3,4-difluoro-5-nitrotrifluoromethylbenzene containing dimethylformamideas a yellow oil, as the first distilling component (0.18 g); 'H NMR δ(CDCl₃) 8.2 (1H, m) and 7.83 (1H, m).

PREPARATION 8

This description illustrates the preparation of3-amino-5-chloro-4-fluorotrifluoromethylbenzene.

5-Chloro-4-fluoro-3-nitrotrifluoromethylbenzene (50 g) was added to acooled (5° C.) solution of stannous chloride (140 g) in concentratedagueous hydrochloric acid (187 ml). After stirring for several hours atthe ambient temperature (ca 22° C.), the reaction mixture was stoodovernight. After basification by the addition of sodium hydroxide, thereaction mixture was extracted with ethyl acetate. The organic layer waswashed with water, dried, and the solvent removed by evaporation underreduced pressure. The residual yellow oil was kugelrohr distilled underreduced pressure to give 3-amino-5-chloro-4-fluorotrifluoromethylbenzene(32 g):bp. 105° C./11 mm Hg; 'H NMR δ (CDCl₃) 7.03 (1H, dq), 6.90 (1H,dq).

PREPARATION 9

This description illustrates the preparation of3-chloro-4-fluoro-5-iodotrifluoromethylbenzene.

3-Amino-5-chloro-4-fluorotrifluoromethylbenzene (10 g) was addeddropwise to a stirred suspension of t-butylnitrite (25 g) and copper (I)iodide (9 g) in dry acetonitrile (185 ml) whilst the temperature wasmaintained at 0° C. After the addition was complete the stirred reactionmixture was kept at 0° C. for a further 2 hours, after which it wasallowed to warm to ambient temperature. After the addition of diluteagueous hydrochloric acid, the reaction mixture was extracted intoether, the organic layer throughly washed with agueous sodiummetabisulphite solution, and dried over anhydrous magnesium sulphate.Removal of the solvent by evaporation under reduced pressure gave abrown oil, which was purified by chromotography on silica gel with amixture of 5% ethyl acetate (by volume) in n-hexane as eluent. The firsteluting component was collected to give3-chloro-4-fluoro-5-iodotrifluoromethylbenzene as a pale yellow oil(5.66 g);

'H NMR δ (CDCl₃) 7.8 (1H, m) and 7.65 (1H, m); ¹⁹ F NMR δ (CDCl₃) -63.96(3F, s) and -89.48 (1F, s).

PREPARATION 10

The following compound was prepared according to the general method ofPreparation 3 from appropriate compounds of formula (III).

5-Bromo-4-pentafluoroethylpyrimidin-6-one (mp. 165°-166.5° C.);

'H NMR δ (CDCl₃) 13.6 (1H, brs) and 8.35 (1H, s).

PREPARATION 11

This description illustrates the preparation of5-chloro-4-pentafluoroethylpyrimidin-6-one.

A solution of 4-pentafluoroethylpyrimidin-6-one (0.4 g) andN-chlorosuccinimide (0.27 g) in dry dimethylformamide (5 ml) was heatedto 80° C. for 3 hours. After cooling to ambient temperature, thereaction mixture was poured into water, and extracted into ethylacetate. The organic layer was dried, over anhydrous magnesium sulphate,filtered, and evaporation of the solvent under reduced pressure gave abrown oil. Recrystallisation from water gave5-chloro-4-pentafluoroethylpyrimidin-6-one

'H NMR δ(CDCl₃) 8.22 (s).

PREPARATION 12

This description illustrated the preparation of4-difluoromethylpyrimidin-6-one.

Thiourea was reacted with chloro-difluoro acetoacetate in the presenceof sodium methoxide according to the manner illustrated inPreparation 1. The crude material so formed was then reacted with Raneynickel according to the manner illustrated in Preparation 2. The orangeproduct so formed was identified as a mixture of components, containing75% (by G.L.C. analysis) of 4-difluoromethylpyrimidin-6-one.

'H NMR δ (CDCl₃ +1 drop DMSO) 8.10 (1H, s), 6.70 (1H, s) and 6.38 (1H,t).

This material was used without further purification.

PREPARATION 13

This description illustrated the preparation of3,4-dibromo-5-nitrotrifluoromethylbenzene.

4-Amino-3-bromo-5-nitrotrifluoromethylbenzene (10 g) in acetonitrile (7ml) was added dropwise to a stirred suspension of t-butylnitrite (18.6g) and copper (II) bromide (10 g) in dry acetonitrile (138 ml) whilstthe temperature was maintained at 0° C. After the addition was completethe stirred reaction mixture was kept at 0° C. for a further 2 hours,after which time it was allowed to warm to ambient temperature. Thereaction mixture was poured into dilute agueous hydrochloric acid andextracted into diethyl ether. The organic layer was throughly washedwith water and brine and dried over anhydrous magnesium sulphate.Filtration and evaporation of the solvent under reduced pressure gave ayellow oil which was subjected to kugelrohr distillation to give3,4-dibromo-5-nitrotrifluoromethylbenzene as a yellow oil, whichsolidified on cooling. B.p. 140° C. at 15 mm Hg).

'H NMR δ (CDCl₃) 8.10 (1H, d) and 7.90 (1H, d).

EXAMPLE 1

This Example illustrates the preparation of1-(2,6-dichloro-4-trifluoromethyl)-4-trifluoromethylpyrimidin-6-one(Compound 1 in Table I).

A dry reaction flask was purged with nitrogen and charged with a 50%suspension of sodium hydride (1.6 g). The sodium hydride was washed withpentane and suspended in dimethylformamide (DMF, 20 ml). A solution of6-trifluoromethylpyrimidin-4-one (5 g) in DMF (30 ml) was addeddropwise. When the addition was complete the reaction was stirred for afurther fifteen minutes, then 3,5-dichloro-4-fluorobenzotrifluoride (28g) was added in one portion and the mixture heated at 100° C. for sixhours. The reaction mixture was allowed to cool, poured into brine, andextracted with ethyl acetate. The organic layer was washed with brine,dried over magnesium sulphate and evaporated in vacuo to give a brownresidue which was purified by chromotography on silica gel using 20%diethyl ether/petrol as eluent to give (compound 1 in Table I) (812 mg).

'H NMR δ (CDCl₃) 8.0 (1H,s), 7.8 (2H,s), 7.0 (1H,s).

EXAMPLE 2

The following compounds were prepared according to the general method ofExample 1 from appropriate compounds of formula II and formula III.

(a)1-(2-Chloro-6-nitro-4-trifluoromethylphenyl)-4-trifluoromethylpyrimidin-6-one(Compound 2 in Table I) mp. 149°-150° C.;

'H NMR: δ (CDCl₃) 8.4 (1H,m), 8.2 (1H,m), 8.1 (1H,s), 7.0 (1H,s).

(b)1-(2-Fluoro-6-chloro-4-trifluoromethylphenyl)-4-trifluoromethylpyrimidin-6-one(Compound 4 in Table I).

'H NMR δ (CDCl₃) 8.08 (1H, s), 7.74 (1H, s), 7.55 (1H, d), 6.98 (1H, s).

(c)1-(2-Bromo-6-chloro-4-trifluoromethylphenyl)-4-trifluoromethylpyrimidin-6-one(Compound 5 in Table I) mp. 172°-174.8° C.;

'H NMR: δ (CDCl₃) 8.03 (1H, s), 7.99 (1H, s), 7.84 (1H, s), 7.00 (1H,s).

(d)1-(2,6-Dibromo-4-trifluromethylphenyl)-4-trifluoromethylpyrimidin-6-one(Compound 6 in Table I) mp. 177.6°-179.8° C.

NMR: δ (CDCl₃) 8.08 (2H, s), 7.98 (1H, s) 7.00 (1H, s).

(e)1-(2-Chloro-4-trifluoromethyl-6-nitrophenyl)-4-pentafluoroethylpyrimidin-6-one(Compound no 17 in Table I); except that the reaction was heated to 100°C. for 4 hours. The compound showed a mp. 145°-146.5° C.;

'H NMR δ (CDCl₃) 8.45 (1H, s), 8.21 (1H, s), 8.11 (1H, s) and 7.02 (1H,s).

(f)1-(2,6-Dichloro-4-trifluoromethylphenyl)-4-pentafluoroethylpyrimidin-6-one(Compound 18 in Table I); except that the reaction was heated to 100° C.for 16 hours. The compound showed mp. 168.7°-169.8° C.;

'H NMR δ (CDCl₃) 8.00 (1H, s), 7.82 (2H, s) and 7.05 (1H, s).

(g)1-(2,6-Difluoro-4-trifluoromethylphenyl)-4-trifluoromethylpyrimidin-6-one(Compound 11 in Table I); except that a four fold excess of arylfluoride was used, and the reaction mixture was heated at 90° C. for 36hours.

'H NMR δ (CDCl₃) 8.12 (1H, s), 7.48 (2H, d) and 6.98 (1H,s).

(h) 1-(2-Chloro-6-iodo-4-trifluoromethylphenyl)4-trifluoromethylpyrimidin-6-one (Compound 10 in Table I); except thatthe reaction was heated to 90° C. for 16 hours.

'H NMR δ (CDCl₃) 8.15 (s, 1H), 7.95 (s, 1H), 7.85 (s, 1H) and 7.0 (s,1H); ¹⁹ F NMR δ (CDCl₃) -63.6 (3F, s) and -72.0 (3F, s).

(i) 1-(2-Fluoro-6-nitro-4-trifluoromethylphenyl)-4-trifluoromethylpyrimidin-6-one (Compound 20 in Table I); except thatthe reaction mixture was maintained at the ambient temperature for 2hours. The compound showed mp. 147°-151° C.

'H NMR δ (CDCl₃) 8.38 (1H, s), 8.37 (1H, s); 7.97 1H, d) and 6.98 (1H,s).

(j)1-(2-Bromo-6-nitro-4-trifluoromethylphenyl)-4-trifluoromethylpyrimidin-6-one(Compound 21 in Table I); except that the reaction was heated at 75° C.for 16 hours. The compound showed mp. 128°-130° C.

'H NMR δ (CDCl₃) 8.45 (1H, d), 8.35 (1H, d), 8.10 (1H, s) and 6.95 (1H,s). In this Example R⁷ in formula (II) represents bromine.

(k)1-(2,6-Dichloro-4-trifluoromethylphenyl)-5-bromo-4-trifluoromethylpyrimidin-6-one(Compound 9 in Table I); except that the reaction mixture was heated 75°C. for 6 hours, followed by heating at 90° C. for 24 hours. The compoundshowed mp. 167°-168° C.

'H NMR δ (CDCl₃) 7.95 (1H, s) and 7.82 (2H, s); ¹⁹ F NMR δ (CDCl₃)-63.80 (3F, s) and -67.45 (3F, s).

(1)1-(2,6-Dinitro-4-trifluoromethylphenyl)-5-bromo-4-trifluoromethylpyrimidin-6-one(Compound 15 in Table I); except that the reaction mixture wasmaintained at ambient temperature for 16 hours. The compound showed mp.199.5°-202° C.

'H NMR δ (CDCl₃) 8.8 (2H, s) and 8.45 (1H, s).

(m)1-(2,Chloro-6-nitro-4-trifluoromethyl)-5-chloro-4-trifluoromethylpyrimidin-6-one(compound 12 in Table I); except that the reaction mixture was stirredat the ambient temperature for 2 hours. The compound showed mp 145°-147°C.

'H NMR δ (CDCl₃) 8.5 (1H, s), 8.25 (1H, s) and 8.2 (1H, s).

(n)1-(2,6-dichloro-4-trifluoromethyl)-5-chloro-4-trifluoromethylpyrimidin-6-one(Compound 13 in Table I); except that the reaction mixture was heated at85° C. for a period of 20 hours. The compound showed mp. 166°-168° C.

'H NMR δ (CDCl₃) 7.95 (1H, s) and 7.85 (2H, s).

(o)1-(2-bromo-6-nitro-4-trifluoromethylphenyl)-5-chloro-4-trifluoromethylpyrimidin-6-one(compound 25 in Table I); except that the reaction mixture was heated to90° C. for 5 hours. The compound showed mp. 136.5°-138° C.

'H NMR δ (CDCl₃) 8.50 (1H, s), 8.38 (1H, s) and 8.02 (1H, s). In thisexample R⁷ in formula (II) represents bromine.

(p)1-(2-chloro-6-fluoro-4-trifluoromethylphenyl)-5-chloro-4-trifluoromethylpyrimidin-6-one(compound 22 in Table I); except that the reaction mixture was heated to90° C. for 40 hours.

'H NMR δ (CDCl₃) 8.98 (1H, s), 7.74 (1H, s) and 5.57 (1H, d).

(g)1-(2-Bromo-6-chloro-4-trifluoromethyl)-5-chloro-4-trifluoromethylpyrimidin-6-one(Compound 34 in Table I).

'H NMR δ (CDCl₃) 8.00 (1H, s), 7.93 (1H, s), 7.88 (1H, s).

(r)1-(2,6-Dibromo-4-trifluoromethyl)-5-chloro-4-trifluoromethylpyrimidin-6-one(Compound 31 in Table I); except that the reaction mixture was heated at90° C. for 16 hours. The compound showed mp. 160°-161° C.

'H NMR δ (CDCl₃) 8.03 (2H, s), 7.91 (1H, s).

(s)1-(2-Bromo-6-chloro-4-trifluoromethyl)-5-bromo-4-trifluoromethylpyrimidin-6-one(Compound 30 in Table I); except that the reaction mixture was heated to85° C. for 16 hours. The compound showed mp. 166°-168° C.

'H NMR δ (CDCl₃) 7.98 (1H, s), 7.92 (1H, s), 7.88 (1H, s).

(t)1-(2-Chloro-6-nitro-4-trifluoromethyl)-5-cyano-4-trifluoromethylpyrimidin-6-one(Compound 27 in Table I); except that the reaction mixture wasmaintained at the ambient temperature for 18 hours. The compound showedmp. 168.7°-169.2° C.

'H NMR δ (CDCl₃) 8.50 (1H, 0), 8.26 (1H, S), 8.24 (1H, d).

(u)1-(2,6-Dichloro-4-trifluoromethyl)-5-cyano-4-trifluoromethylpyrimidin-6-one(Compound 28 in Table I); except that the reaction mixture was heated to100° C. for 23 hours.

'H NMR δ (CDCl₃) 8.19 (1H, s), 7.85 (2H, s).

(v) 1-(2,6-dichloro-4-trimethylfluorophenyl)-4-chloropyrimidin-6-one(compound 35 in Table 1); except that the reaction mixture was heated to90° C. for 27 hours. The compound showed mp. 119.1°-122° C.

'H NMR δ (CDCl₃) 7.84 (1H, s); 7.80 (2H, s) and 6.7 (1H, s).

(w)1-(2-chloro-6-fluoro-4-trifluoromethylphenyl)-4-pentafluoroethylpyrimidin-6-one(compound 38 in Table I); except that the reaction was heated to 90° C.for 23 hours and a four fold excess of the aryl fluoride was used. Thecompound showed mp. 121°-122.8° C.

'H NMR δ (CDCl₃) 8.05 (1H, s), 7.75 (1H, s), 7.58 (1H, dd) and 7.06 (1H,s).

(x)1-(2,6-Difluoro-4-trifluoromethyl)-5-chloro-4-trifluoromethylpyrimidin-6-one(compound no 39 in Table 1), except that the reaction mixture was heatedto 90° C. for 48 hours.

'H NMR δ (CDCl₃) 8.05 (1H, s) and 7.5 (2H, d).

(y)1-(2-Bromo-6-chloro-4-trifluoromethyl)-4-pentafluoromethylpyrimidin-6-one(compound no 42 in Table 1), except that the reaction mixture was heatedto 90° C. for 16 hours. The compound showed m.p. 172°-173° C.

'H NMR δ (CDCl₃) 8.00 (2H, brs), 7.88 (1H, s) and 7.08 (1H, s).

(z) 1-(2,6-dibromo-4-trifluoromethyl)-4-pentafluoroethylpyrimidin-6-one(compound no 45 in Table 1) except that the reaction mixture was heatedto 90° C. for 16 hours. The compound showed m.p. 175.8°-176.2° C.

'H NMR δ (CDCl₃) 8.05 (2H, s), 7.98 (1H, s) and 7.06 (1H, s).

(aa)1-(2,6-dichloro-4-trifluoromethyl)-5-chloro-4-pentafluoromethylpyrimidin-6-one(compound no 46 in Table 1) except that the reaction mixture was heatedto 90° C. for 16 hours.

'H NMR δ (CDCl₃) 7.9 (1H, s) and 7.82 (1H, s).

The product was shown by G.L.C. analysis is to contain 10% of1-(2,6-dichloro-4-trifluoromethyl-4-pentafluoroethylpyrimidin-6-one asan impurity.

EXAMPLE 3

This Example illustrates an alternative preparation of1-(2-Chloro-6-nitro-4-trifluoromethylphenyl)-4-trifluoromethylpyrimidin-6-one(Compound 2 in Table I).

A dry reaction flask was purged with nitrogen and charged with a 50%suspension of sodium hydride (640 mg). The sodium hydride was suspendedin DMF (20 ml). Solid 6-trifluoromethylpyrimidin-6-one (2 g, 12 mmol)was added portionwise, the mixture stirred for a further 10 minutes, andthen 3-chloro-4-fluoro-5-nitrobenzotrifluoride (3.3 g) was added in oneportion. The deep-red reaction mixture was vigorously stirred for tenminutes and then poured into water and extracted rigorously with ether.The combined ethereal layers were washed with water, then brine, anddried over magnesium sulphate. The solvent was removed under reducedpressure to afford a yellow residue which was recrystallised from amixture of ethyl acetate and hexane to give1-(2-chloro-6-nitro-4-trifluoromethylphenyl)-4-trifluoromethylpyrimidin-6-oneas yellow crystals (2.3 g), mp 149°-150° C., and NMR spectrum as before.

EXAMPLE 4

The following compounds were prepared according to the general method ofExample 3 from appropriate compounds of formula II and formula III.

(a)1-(2,6-Dinitro-4-trifluoromethylphenyl)-4-trifluoromethylpyrimidin-6-one(Compound 3 in Table I) mp 194°-197.6° C.

'H NMR δ(CDCl₃) 8.82 (2H, s), 8.60 (1H, s), 6.95 (1H, s).

(b)1-(2-Chloro-4-nitro-4-trifluoromethylphenyl)-5-fluoro-4-trifluoromethylpyrimidin-6-one(Compound 7 in Table I).

'H NMR δ (CDCl₃) 8.48 (1H, s), 8.24 (1H, s), 7.92 (1H, s).

(c)1-(2-Chloro-6-nitro-4-trifluoromethylphenyl)-5-bromo-4-trifluoromethylpyrimidin-6-one(Compound 8 in Table I) mp. 141°-142° C.

'H NMR: δ (CDCl₃): 8.45 (1H, s), 8.20 (2H, s), 8.05 (1H, s).

(d)1-(2,6-dinitro-4-trifluoromethylphenyl)-5-chloro-4-trifluoromethylpyrimidin-6-one(Compound 24 Table I); except that the reaction mixture was maintainedat room temperature for 16 hours. The compound showed mp. 190°-193° C.

'H NMR δ (CDCl₃ +3 drops DMSO) 8.85 (2H, s) and 8.60 (1H, s).

(e)1-(2-chloro-6-nitro-4-trifluoromethylphenyl)-5-iodo-4-trifluoromethylpyrimidin-6-one(Compound 14 Table I); except that the reaction mixture was maintainedat room temperature for 1 hour. The compound showed mp. 151°-153° C.

'H NMR δ (CDCl₃) 8.44 (1H fine d), 8.20 (1H, fine d) and 7.98 (1H, s).

(f) 1-(2-chloro-6-nitro-4-trifluoromethylphenyl)-4-chloropyrimidin-6-one(compound 36 in Table I); except that the reaction mixture wasmaintained at ambient termperature for 2 hours. The compound showed mp.170.5°-172.1° C.

'H NMR δ (CDCl₃) 8.40 (1H, s); 8.20 (1H, s), 7.95 (1H, s) and 6.68 (1H,s).

(g)1-(2-chloro-6-nitro-4-trifluoromethylphenyl)-5-chloro-4-pentafluoroethylpyrimidin-6-one(compound no 37 in Table I); except that the reaction mixture wasmaintained at room temperature for 2 hours. The compound showed mp.170°-171.2° C.

'H NMR δ (CDCl₃) 8.46 (1H, d), 8.22 (1H, d), 8.00 (1H, s).

(h)1-(2-Chloro-6-nitro-4-trifluoromethylphenyl)-4-difluoromethylpyrimidin-6-one(compound no 41 in Table I); except that the reaction mixture wasmaintained at ambient temperature for 1.5 hours. The compound showed mp.130°-132° C.

'H NMR δ (CDCl₃) 8.41 (1H, d), 8.19 (1H, d), 8.05 (1H, s), 6.90 (1H, s)and 6.47 (1H, t).

(i)1-(2-Bromo-6-nitro-4-trifluoromethyl)-4-pentafluoroethylpyrimidin-6-one(compound no 44 in Table I); except that the reaction mixture wasmaintained at ambient temperature for 1 hour. The compound showed m.p.138°-139° C.

'H NMR δ (CDCl₃) 8.48 (1H, d), 8.38 (1H, d), 8.10 (1H, s) and 7.02 (1H,s).

EXAMPLE 5

This Example illustrates the preparation of1-(3-chloro-2,6-dinitro-4-trifluoromethylphenyl)-4-trifluromethylpyrimidin-6-one(Compound 16 in Table I.).

A mixture of 4-trifluoromethylpyrimidin-6-one (0.48 g),2,4-dichloro-3,5-dinitrotrifluorobenzene (0.9 g) and potassium carbonate(0.41 g) in dry dimethylformamide (10 ml) was vigorously stirred atambient temperature for a period of 15 minutes. The reaction mixture wasthen poured into water, and extracted into ethyl acetate. After dryingand evaporation of the solvent, under reduced pressure, the residue wassubjected to chromatography on silica gel using 30% (by volume)ethylacetate in petroleum ether (boiling range 60°-80° C.) as eluent.The required fractions were combined, and the solvent removed underreduced pressure to give a yellow solid, which was then triturated withpetroleum ether (boiling range 60°-80° C.). The solid was dissolved inboiling ethanol, filtered, and the solvent removed under reducedpressure. The residue was again triturated with petroleum ether (boilingrange 60°-80° C.) and finally recrystallised from petroleum ether(boiling range 60°-80° C.) containing ethylacetate (9% by volume) togive1-(3-chloro-2,6-dinitro-4-trifluoromethylphenyl)-4-trifluoromethylpyrimidin-6-oneas a yellow solid:

'H NMR δ (CDCl₃) 8.8 (1H, s), 8.1 (1H, s) and 6.95 (1H, s).

EXAMPLE 6

This Example illustrates the preparation of1-(2-Chloro-6-fluoro-4-trifluoromethyl)-5-bromo-4-trifluoromethylpyrimidin-6-one(Compound 19 in Table I).

5-Chloro-3,4-difluorotrifluoromethylbenzene was reacted with5-bromo-4-trifluoromethylpyrimidin-6-one according to the proceduregiven in Example 1. The resultant product was then reacted with amixture of bromine (0.leg) and sodium acetate (0.3 eq) in acetic acidfor 16 hours. The reaction mixture was then poured into water, andextracted with ethyl acetate. The organic layer was washed with agueoussodium bicarbonate solution, followed by agueous sodium thiosulphatesolution and finally brine. After drying and filtration, evaporation ofthe solvent under reduced pressure gave1-(2-chloro-6-fluoro-4-trifluoromethyl)-5-bromo-4-trifluoromethylpyrimidin-6-oneas a pale orange solid mp. 122°-125° C.

'H NMR δ (CDCl₃) 8.00 (1H, s); 7.74 (1H, s) and 7.55 (1H, d).

EXAMPLE 7

This Example illustrates the preparation of1-(2,6-difluoro-4-trifluoromethylphenyl)-5-bromo-4-trifluoromethylpyrimidin-6-one(compound 23 in Table I).

A solution of bromine (146 mg) in acetic acid (1 ml) was added dropwiseto a solution of compound 11 (in Table I) (285 mg) and sodium acetate(204 mg) in acetic acid (3 ml). After stirring at the ambienttemperature for 16 hours, the solvent was removed by evaporation underreduced pressure and the residue dissolved in agueous sodium bicarbonatesolution. After extraction with ethyl acetate, the organic layer waswashed with agueous sodium thiosulphate solution, dried and filtered,and concentrated under reduced pressure to give a pale yellow solid.Recrystallization from a mixture of ethyl acetate and petroleum ether(boiling range 60°-80° C.) gave1-(2,6-difluoro-4-trifluoromethylphenyl)-5-bromo-4-trifluoromethylpyrimidin-6-one;

'H NMR δ (CDCl₃) 8.05 (1H, s) and 7.48 (2H, d).

EXAMPLE 8

The following compounds were prepared according to the general method ofExample 7 from the appropriate compounds of formula I.

(a)1-(2-bromo-6-nitro-4-trifluoromethyl)-5-bromo-4-trifluoromethylpyrimidin-6-one(Compound 26 in Table I). The compound showed mp. 139°-141° C.

'H NMR δ (CDCl₃) 8.50 (1H, m), 8.38 (1H, m) and 8.02 (1H, m).

(b)1-(2,6-Dichloro-4-trifluoromethyl)-5-bromo-4-pentafluoroethylpyrimidin-6-one(Compound 33 in Table 1). The compound showed mp. 140.5°-141.5° C.

'H NMR δ (CDCl₃) 7.92 (1H, s) and 7.83 (2H, s).

(c)1-(2-Chloro-6-fluoro-4-trifluoromethyl)-5-bromo-4-pentafluoroethylpyrimidin-6-one(compound no 40 in Table I) The compound showed mp. 94°-96° C.

'H NMR δ (CDCl₃) 8.00 (1H, s), 7.78 (1H, s) and 7.58 (1H, d).

(d)1-(2-Chloro-6-bromo-4-trifluoromethyl)-5-bromo-4-pentafluoroethylpyrimidin-6-one(compound no 43 in Table I). The compound showed mp. 148.5°-149.5° C.

'H NMR δ (CDCl₃) 7.99 (1H, d), 7.90 (1H, s) and 7.87 (1H, d).

(e)1-(2,6-dibromo-4-trifluoromethyl)-5-bromo-4-pentafluoroethylpyrimidin-6-one(compound no 47 in Table I). The compound showed mp. 158°-159.5° C.

' H NMR δ (CDCl₃) 8.02 (2H, s) and 7.90 (1H, s).

(f)1-(2,6-Dibromo-4-trifluoromethyl)-5-bromo-4-trifluoromethylpyrimidin-6-one(compound 34 in Table I). The compound showed mp 163.5°-164.5° C.

'H NMR δ (CDCl₃) 8.03 (2H, s), 7.92 (1H, s).

EXAMPLE 9

The following compound was prepared according to the general method ofExample 6 from the appropriate compounds.

(a)1-(2-Chloro-6-nitro-4-trifluoromethyl)-5-bromo-4-pentafluoroethylpyrimidin-6-one(Compound 29 in Table I). The compound showed mp. 178°-181° C.

'H NMR δ (CDCl₃) 8.46 (1H, d), 8.21 (1H, d) and 8.02 (1H, s).

EXAMPLE 10

This Example illustrates the insecticidal properties of the compounds offormula (I).

The activity of the compounds was determined using a variety of insectpests. The compound was used in the form of liguid preparationscontaining parts per million (ppm) by weight of the compound. Thepreparations were made by dissolving compound the cin acetone anddiluting the solutions water with containing 0.01% by weight of awetting sold agentunder the trade name "SYNPERONIC" NX until iguid thelpreparations contained the required ntration of concethe Product."SYNPERONIC" is a Registered Trade Mark.

The test procedure adopted with regard to each pest was basically thesame and comprised supporting a number of the pests on a medium whichwas usually a host plant or a foodstuff on which the pests feed, andtreating either or both the pests and the medium with the preparations.The mortality of the pests was then assessed at periods usually varyingfrom one to three days after the treatment.

The results of the tests are given in Table II for the compounds, at therate in parts per million given in the second column as a grading ofmortality designated as 9, 5 or 0 wherein 9 indicates 80-100% mortality,5 indicates 50-79% mortality and 0 indicates less than 50% mortality.

In Table III the pest organism used is designated by a letter code andthe pest species, the support medium or food, and the type and durationof test is given.

In similar tests, certain compounds of formula (I) showed activityagainst Nephotettix Cincticeps (green leaf hopper-nymphs), Spodopteraexiqua (lesser army worm-larvae) and Heliothis virescens (tobaccobudworm-larvae).

                  TABLE II                                                        ______________________________________                                                  RATE OF      SPECIES                                                          APPLICATION  MD      BG                                             COMPOUND    ppm            (see Table III)                                    ______________________________________                                         1          500            9       9                                           2          500            9       9                                           4          500            9       9                                           5          500            9       9                                           6          500            9       9                                           8          500            0       5                                           9          500            5       9                                          10          500            9       9                                          11          500            9       9                                          12          500            0       9                                          13          500            9       9                                          14          500            9       9                                          15          500            5       0                                          17          500            9       9                                          18          500            9       9                                          19          500            9       9                                          20          500            9       9                                          21          500            9       9                                          22          500            9       9                                          23          500            0       9                                          25          500            5       9                                          26          500            9       5                                          27          500            9       9                                          28          500            9       9                                          29          500            0       5                                          30          500            0       9                                          31          500            0       9                                          32          500            0       9                                          33          500            0       9                                          34          500            0       9                                          37          500            9       9                                          38          500            9       9                                          39          500            9       9                                          40          500            9       9                                          41          500            9       0                                          42          500            9       9                                          43          500            9       9                                          44          500            9       9                                          45          500            9       9                                          46          500            9       9                                          47          500            9       9                                          ______________________________________                                         A dash indicates not tested.                                             

A dash indicates not tested.

                  TABLE III                                                       ______________________________________                                                          SUPPORT                                                     CODE              MEDI-                                                       LETTERS TEST      UM/       TYPE OF DURATION                                  (Table II)                                                                            SPECIES   FOOD      TEST    (Days)                                    ______________________________________                                        BG      Blattella Plastic pot                                                                             Residual                                                                              3                                                 germanica                                                                     (Cockroach                                                                    nymphs)                                                               MD      Musca     Cotton    Contact 1                                                 domestica wool/sugar                                                          (house-                                                                       flies -                                                                       adults)                                                               ______________________________________                                         "Contact" test indicates that both pests and medium were treated and          "Residual" indicates that the medium was treated before infestation with      the pests.                                                               

We claim:
 1. A compound of formula (I): ##STR14## wherein R¹ and R² areindependently selected from halogen or nitro; R³ and R⁴ areindependently selected from hydrogen or halogen; R⁵ is hydrogen, halogenor cyano; and R⁶ is halogen or haloalkyl; provided that R¹, R², R³ andR⁴ are not all fluorine.
 2. A compound according to claim 1 where atleast one of R¹ and R² is fluoro, chloro, bromo or iodo.
 3. A compoundaccording to claim 2 where R¹ and R² are both chloro.
 4. A compoundaccording to claim 2 where R¹ and R² are both fluoro.
 5. A compoundaccording to claim 1 wherein R⁶ is trifluoromethyl or pentafluoroethyl.6. A compound according to claim 5 where R⁵ is hydrogen, chlorine orbromine.
 7. A compound according to claim 1 of formula (IA) ##STR15##one of wherein R^(1') or R^(2') is halo and the other is halogen ornitro; R^(5') is hydrogen or halogen; and R^(6') is trifluoroethyl orpentafluoroethyl.
 8. A method of killing or controlling insect oracarine pests which method comprises applying to the pest or to a locusthereof a insecticidally or acaricidally effective amount of a compoundof formula (I) as defined in claim
 1. 9. An insecticidal or acaricidalcomposition comprising a compound of formula (I) according to claim 1 incombination with a diluent or carrier.
 10. A compound of formula (IV):##STR16## wherein R³ is hydrogen or halogen; R⁵ is hydrogen, halogen orcyano; R⁶ is halogen or haloalkyl; and R⁷ is halogen or nitro; R⁸ and R⁹are amino, halogen or nitro provided that at least one of R⁸ or R⁹ isamino.